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5th handbook of transfusion medicine

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5th handbook of transfusion medicine

  1. 1. Handbook of Transfusion Medicine Editor: Dr Derek Norfolk United Kingdom Blood Services 5th edition
  2. 2. Handbook of Transfusion Medicine Editor: Dr Derek Norfolk United Kingdom Blood Services 5th edition
  3. 3. Published by TSO and available from: Online www.tsoshop.co.uk Mail, Telephone, Fax & E-mail TSO PO Box 29, Norwich NR3 1GN Telephone orders/General enquiries: 0870 600 5522 Fax orders: 0870 600 5533 E-mail: customer.services@tso.co.uk Textphone: 0870 240 3701 TSO@Blackwell and other Accredited Agents Editor Dr Derek Norfolk c/o Caroline Smith JPAC Manager NHS Blood and Transplant Longley Lane SHEFFIELD S5 7JN Email: caroline.smith@nhsbt.nhs.uk © Crown Copyright 2013 All rights reserved. You may re-use this information (excluding logos) free of charge in any format or medium, under the terms of the Open Government Licence. To view this licence, visit http://www.nationalarchives.gov.uk/ doc/open-government-licence/ or e-mail: psi@nationalarchives.gsi.gov.uk Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. Applications for reproduction should be made in writing to The National Archives, Kew, Richmond, Surrey TW9 4DU. e-mail: psi@nationalarchives.gsi.gov.uk First published 2013 ISBN 9780117068469 Printed in the United Kingdom by The Stationery Office.
  4. 4. iii Contents List of figures ix List of tables xi Preface xiii 1 Transfusion ten commandments 1 2 Basics of blood groups and antibodies 5 2.1 Blood group antigens 7 2.2 Blood group antibodies 7 2.3 Testing for red cell antigens and antibodies in the laboratory 7 2.4 The ABO system 8 2.4.1 Transfusion reactions due to ABO incompatibility 8 2.5 The Rh system 9 2.6 Other clinically important blood group systems 10 2.7 Compatibility procedures in the hospital transfusion laboratory 10 2.7.1 Group and screen 10 2.7.2 Compatibility testing 10 2.7.3 Electronic issue 11 2.7.4 Blood for planned procedures 11 3 Providing safe blood 13 3.1 Blood donation 15 3.1.1 Donor eligibility 16 3.1.2 Frequency of donation 16 3.1.3 Genetic haemochromatosis 16 3.2 Tests on blood donations 16 3.2.1 Screening for infectious agents 16 3.2.2 Precautions to reduce the transfusion transmission of prion-associated diseases 17 3.2.3 Blood groups and blood group antibodies 17 3.2.4 Molecular blood group testing 17
  5. 5. iv Handbook of Transfusion Medicine 3.3 Blood products 17 3.3.1 Blood components 18 3.3.2 Labelling of blood components 18 4 Safe transfusion – right blood, right patient, right time and right place 27 4.1 Patient identification 31 4.2 Documentation 32 4.3 Communication 33 4.4 Patient consent 33 4.5 Authorising (or ‘prescribing’) the transfusion 33 4.6 Requests for transfusion 34 4.7 Pre-transfusion blood sampling 34 4.8 Collection of blood components and delivery to clinical areas 35 4.9 Receiving blood in the clinical area 35 4.10 Administration to the patient 36 4.11 Monitoring the transfusion episode 36 4.12 Technical aspects of transfusion 37 4.12.1 Intravenous access 37 4.12.2 Infusion devices 38 4.12.3 Rapid infusion devices 38 4.12.4 Blood warmers 38 4.12.5 Compatible intravenous fluids 38 4.12.6 Co-administration of intravenous drugs and blood 38 4.13 Transfusion of blood components 39 5 Adverse effects of transfusion 41 5.1 Haemovigilance 43 5.2 Non-infectious hazards of transfusion 44 5.2.1 Acute transfusion reactions 44 5.2.2 Severe and life-threatening reactions 45 5.2.3 Less severe acute transfusion reactions 53 5.2.4 Delayed transfusion reactions 53
  6. 6. v Contents 5.3 Infectious hazards of transfusion 55 5.3.1 Viral infections 55 5.3.2 Bacterial infections 58 5.3.3 Protozoal infections 59 5.4 Variant Creutzfeldt–Jakob disease (vCJD) 59 6 Alternatives and adjuncts to blood transfusion 61 6.1 Autologous blood transfusion (collection and reinfusion of the patient’s own red blood cells) 63 6.1.1 Predeposit autologous donation (PAD) 63 6.1.2 Intraoperative cell salvage (ICS) 64 6.1.3 Postoperative cell salvage (PCS) 65 6.1.4 Acute normovolaemic haemodilution (ANH) 66 6.2 Pharmacological measures to reduce transfusion 66 6.2.1 Antifibrinolytic and procoagulant drugs 66 6.2.2 Aprotinin 67 6.2.3 Tissue sealants 67 6.2.4 Recombinant activated Factor VII (rFVIIa, NovoSeven™) 67 6.2.5 Desmopressin (DDAVP) 68 6.2.6 Erythropoiesis stimulating agents (ESAs) 68 6.3 Thrombopoietin mimetics 69 6.4 Parenteral iron 69 7 Effective transfusion in surgery and critical care 71 7.1 Transfusion in surgery 74 7.1.1 Red cell transfusion 74 7.1.2 Bleeding problems in surgical patients 76 7.1.3 Newer oral anticoagulants 78 7.1.4 Heparins 78 7.1.5 Antiplatelet drugs 78 7.1.6 Systemic fibrinolytic agents 79 7.1.7 Cardiopulmonary bypass 79 7.1.8 Liver transplantation 79 7.2 Transfusion in critically ill patients 80 7.2.1 Red cell transfusion in critical care 80 7.2.2 Platelet transfusion in critical care 80 7.2.3 Plasma component transfusion in critical care 82 7.3 Transfusion management of major haemorrhage 82 7.3.1 Red cell transfusion in major haemorrhage 83 7.3.2 Coagulation and major haemorrhage 85 7.3.3 Platelets and major haemorrhage 86 7.3.4 Pharmacological treatments in major haemorrhage 86 7.3.5 Acute upper gastrointestinal bleeding 86
  7. 7. vi Handbook of Transfusion Medicine 7.3.6 Major obstetric haemorrhage 87 7.3.7 Audit of the management of major haemorrhage 87 8 Effective transfusion in medical patients 89 8.1 Haematinic deficiencies 92 8.1.1 Iron deficiency anaemia 92 8.1.2 Vitamin B12 or folate deficiency 92 8.2 Anaemia of chronic disease (ACD) 92 8.3 Anaemia in cancer patients 93 8.4 Anaemia and renal disease 93 8.5 Transfusion and organ transplantation 93 8.5.1 Renal transplantation 93 8.5.2 Haemolysis after ABO-incompatible solid organ transplantation 94 8.6 Haemoglobinopathies 94 8.6.1 β-thalassaemia major 95 8.6.2 Red cell alloimmunisation in thalassaemia 95 8.6.3 Sickle cell disease 95 8.6.4 Red cell transfusion in sickle cell disease 96 8.6.5 Red cell alloimmunisation in sickle cell disease 97 8.6.6 Hyperhaemolytic transfusion reactions 97 8.7 Transfusion in haemato-oncology 98 8.7.1 Transfusion support for myelosuppressive treatment 98 8.7.2 Red cell transfusion 98 8.7.3 Prophylactic platelet transfusion 98 8.7.4 Refractoriness to platelet transfusion 99 8.7.5 Selection of compatible blood for patients who have received a marrow or peripheral blood HSC transplant from an ABO or RhD-incompatible donor 100 8.7.6 Prevention of transfusion-associated graft-versus-host disease (TA-GvHD) 102 8.7.7 Prevention of cytomegalovirus transmission by transfusion 103 8.7.8 Long-term transfusion support for patients with myelodysplasia 103 8.8 Indications for intravenous immunoglobulin (IVIg) 103 9 Effective transfusion in obstetric practice 105 9.1 Normal haematological values in pregnancy 107 9.2 Anaemia and pregnancy 108 9.2.1 Iron deficiency 108 9.2.2 Folate deficiency 109 9.3 Red cell transfusion in pregnancy 109 9.4 Major obstetric haemorrhage 109
  8. 8. vii Contents 9.5 Prevention of haemolytic disease of the fetus and newborn (HDFN) 110 9.5.1 HDFN due to anti-D 111 9.5.2 Potentially sensitising events 111 9.5.3 Routine antenatal anti-D prophylaxis (RAADP) 112 9.5.4 Anti-D Ig prophylaxis after the birth of a RhD positive baby or intrauterine death 113 9.5.5 Inadvertent transfusion of RhD positive blood 113 10 Effective transfusion in paediatric practice 115 10.1 Fetal transfusion 118 10.1.1 Intrauterine transfusion of red cells for HDFN 118 10.1.2 Intrauterine transfusion of platelets and management of NAIT 119 10.2 Neonatal transfusion 120 10.2.1 Neonatal red cell exchange transfusion 120 10.2.2 Large volume neonatal red cell transfusion 121 10.2.3 Neonatal ‘top-up’ transfusion 121 10.2.4 Neonatal platelet transfusions 123 10.2.5 Neonatal FFP and cryoprecipitate transfusion 123 10.2.6 Neonatal granulocyte transfusion 124 10.2.7 T-antigen activation 124 10.3 Transfusion of infants and children 125 10.3.1 Paediatric intensive care 125 10.3.2 Haemato-oncology patients 125 10.4 Major haemorrhage in infants and children 126 11 Therapeutic apheresis 127 11.1 Therapeutic plasma exchange (TPE) 129 11.1.1 Indications for therapeutic plasma exchange 129 11.1.2 Risks associated with therapeutic plasma exchange 130 11.1.3 Thrombotic thrombocytopenic purpura (TTP) 131 11.2 Therapeutic erythrocytapheresis 131 11.3 Therapeutic leucapheresis 132 11.4 Therapeutic plateletpheresis 132 11.5 Therapeutic extracorporeal photopheresis 132 11.6 Column immunoadsorption 132
  9. 9. viii Handbook of Transfusion Medicine 12 Management of patients who do not accept transfusion 133 12.1 Anxiety about the risks of blood transfusion 135 12.2 Jehovah’s Witnesses and blood transfusion 135 12.3 Mental competence and refusal of transfusion 136 Appendices 139 Appendix 1: Key websites and references 141 Appendix 2: Acknowledgements 147 Abbreviations and glossary 149 Abbreviations 151 Glossary 155 Index 161
  10. 10. ix List of figures Figure 3.1 Production of blood components and blood derivatives 19 Figure 4.1 Identity check between patient and blood component 37 Figure 5.1 Clinical flowchart for the management of acute transfusion reactions 46 Figure 7.1 Guidelines for red cell transfusion in critical care 81 Figure 7.2 Algorithm for the management of major haemorrhage 84
  11. 11. xi List of tables Table 2.1 Distribution of ABO blood groups and antibodies 8 Table 2.2 Choice of group of red cells, platelets, fresh frozen plasma (FFP) and cryoprecipitate according to recipient’s ABO group 9 Table 3.1 Red cells in additive solution 20 Table 3.2 Platelets from pooled buffy coats 21 Table 3.3 Platelets from apheresis donation 21 Table 3.4 Fresh frozen plasma 22 Table 3.5 Solvent detergent plasma (Octaplas® ) 23 Table 3.6 Cryoprecipitate 24 Table 3.7 Buffy coat (granulocytes) 24 Table 3.8 Granulocytes pooled buffy coat derived in additive solution and plasma 25 Table 3.9 Apheresis granulocytes 25 Table 4.1 Safe blood administration 30 Table 4.2 Blood component administration to adults (doses and transfusion rates are for guidance only and depend on clinical indication) 40 Table 5.1 Investigation of moderate or severe acute transfusion reactions 48 Table 5.2 Comparison of TRALI and TACO 51 Table 5.3 Estimated risk per million blood donations of hepatitis B virus, hepatitis C virus and HIV entering the blood supply due to the window period of tests in use, UK 2010–2012 55 Table 5.4 Confirmed viral transfusion-transmitted infections, number of infected recipients and outcomes reported to UK Blood Services 1996–2012 56 Table 6.1 Licensed indications and summary of dosage recommendations for the major erythropoiesis stimulating agents used in blood conservation 68 Table 7.1 Platelet transfusion thresholds in surgery and invasive procedures 76 Table 7.2 Perioperative management of warfarin anticoagulation 77 Table 7.3 Perioperative management of patients on heparins 78 Table 7.4 Suggested indications for platelet transfusion in adult critical care 82
  12. 12. xii Table 7.5 Options for fibrinogen replacement 85 Table 8.1 Normal adult haemoglobins 94 Table 8.2 Indications for red cell transfusion in acute complications of sickle cell disease 96 Table 8.3 Possible indications for elective red cell transfusion in severe sickle cell disease 97 Table 8.4 Causes of platelet refractoriness 100 Table 8.5 Categories of ABO-incompatible HSC transplant 101 Table 8.6 Recommended ABO blood group of components transfused in the early post-transplant period 101 Table 8.7 Indications for irradiated cellular blood components in haemato-oncology patients 102 Table 8.8 High-priority (‘red’) indications for intravenous immunoglobulin – an adequate evidence base and potentially life-saving 104 Table 8.9 ‘Blue’ indications for intravenous immunoglobulin – a reasonable evidence base but other treatment options are available 104 Table 9.1 Screening for maternal red cell alloantibodies in pregnancy 111 Table 9.2 Anti-D Ig for potentially sensitising events in pregnancy 112 Table 10.1 Red cell component for IUT 119 Table 10.2 Platelets for intrauterine transfusion 120 Table 10.3 Red cells for neonatal exchange transfusion 121 Table 10.4 Summary of BCSH recommendations for neonatal top‑up transfusions 121 Table 10.5 Approximate capillary Hb transfusion thresholds used for ‘restrictive’ transfusion policies in studies evaluated by the Cochrane Review 122 Table 10.6 Red cells for small-volume transfusion of neonates and infants 123 Table 10.7 Suggested transfusion thresholds for neonatal prophylactic platelet transfusion (excluding NAIT) 123 Table 11.1 ASFA Category I indications for therapeutic plasma exchange (first-line therapy based on strong research evidence) 130 Table 11.2 ASFA Category II indications for therapeutic plasma exchange (established second-line therapy) 131
  13. 13.  xiii Preface Although the Handbook of Transfusion Medicine has reached a fifth edition, its purpose remains the same – to help the many staff involved in the transfusion chain to give the right blood to the right patient at the right time (and, hopefully, for the right reason). Transfusion is a complex process that requires everyone, from senior doctors to porters and telephonists, to understand the vital role they play in safely delivering this key component of modern medicine. Training and appropriate technological and managerial support for staff is essential, and e-learning systems such as http://www.learnbloodtransfusion.org.uk are freely available. However, SHOT (Serious Hazards of Transfusion) annual reports highlight the importance of a poor knowledge of transfusion science and clinical guidelines as a cause of inappropriate and unnecessary transfusions. The handbook attempts to summarise current knowledge and best clinical practice. Wherever possible it draws upon evidence- based guidelines, especially those produced by the British Committee for Standards in Haematology (BCSH). Each chapter is now preceded by a short list of ‘Essentials’ – key facts extracted from the text. We have much to congratulate ourselves about. Haemovigilance data from SHOT show that blood transfusion in the UK is very safe, with a risk of death of around 3 in 1 000 000 components issued. Transfusion-transmitted infections are now rare events. Lessons from blood transfusion about the importance of patient identification have improved many other areas of medical practice. But not all is well. Six of the nine deaths associated with transfusion in 2012 were linked to transfusion-associated circulatory overload (TACO), emphasising the importance of careful clinical assessment and monitoring. More than half of serious transfusion incidents are still caused by human error, especially in the identification of patients at sampling and transfusion, and each incident is accompanied by 100 near- miss events. Training and competency assessment of practitioners has been only partially effective and innovative solutions such as the use of bedside barcode scanners or transfusion checklists are slowly entering practice. Most UK regions have seen a significant reduction in the use of red cells over the last decade, especially in surgery, but requests for platelet and plasma components continue to rise. Audits show significant variation in transfusion practice between clinical teams and poor compliance with clinical guidelines. Changing clinical behaviour is difficult, but IT-based clinician decision support systems, linked to guidelines, have real potential to improve prescribing of blood components. As we move from eminence-based to evidence-based medicine, good clinical research will be an important tool in effecting change. Since the last edition of the handbook in 2007, there has been an encouraging growth in high-quality research in transfusion medicine, including large randomised controlled trials with major implications for the safe and effective care of patients. These include the seminal CRASH‑2 trial showing the benefit of a cheap and readily available antifibrinolytic treatment (tranexamic acid) in reducing mortality in major traumatic haemorrhage and studies confirming the safety of restrictive red cell transfusion policies in many surgical and critical care patients. High-quality systematic reviews of clinical trials in transfusion therapy are an increasingly valuable resource. Everyone involved in transfusion has a role in identifying clinically important questions that could be answered by further research. Paul Glaziou, professor of evidence-based medicine at Bond University in Australia, talks about the ‘hyperactive therapeutic reflex’ of clinicians and the importance of ‘treating the patient, not the label’. Furthermore, people increasingly want to be involved in decisions
  14. 14. xiv Handbook of Transfusion Medicine about their treatment. In transfusion medicine there is a growing emphasis on careful clinical assessment, rather than a blind reliance on laboratory tests, in making the decision to transfuse and using clinically relevant, patient-centred endpoints to assess the benefits of the transfusion. For example, reducing fatigue and improving health-related quality of life in elderly transfusion-dependent patients is more important than achieving an arbitrary target Hb level. Importantly, although guidelines outline the best evidence on which to base local policies they must always be interpreted in the light of the individual clinical situation. Other major changes since the last edition of the handbook include: ■■ Reduced concern that a major epidemic of variant Creutzfeldt–Jakob disease (vCJD) will occur, although many precautions, such as the importation of all manufactured plasma products and fresh frozen plasma for patients born after 1 January 1996, remain in place. No practical vCJD screening test for blood donations has been developed. ■■ All UK countries have now introduced automated pre-release bacterial screening of platelet components, although the incidence of bacterial transmission had already fallen significantly following better donor arm cleaning and diversion of the first 20–30 mL of each donation. ■■ Implementation of the Blood Safety and Quality Regulations 2005 (BSQR) has led to the development (and inspection) of comprehensive quality systems in hospital transfusion services and the reporting of serious adverse events and reactions to the Medicines and Healthcare Products Regulatory Agency (MHRA). MHRA now works very closely with the SHOT haemovigilance scheme with the objective of improving patient safety. Having edited this fifth edition of the handbook, I am increasingly impressed by the achievements, and fortitude, of my predecessor Dr Brian McClelland in taking the first four through to publication. Colleagues from many disciplines have kindly contributed to or reviewed sections of the handbook (see Appendix 2) but the responsibility for any of the inevitable errors and omissions is mine alone. I would like to thank the members of the JPAC Standing Advisory Committee on Clinical Transfusion Medicine for their support and advice. A special word of thanks is due to Caroline Smith for her skill and good humour in organising so many aspects of the publication process and ensuring I met (most of) the deadlines. As well as the printed edition, the handbook will also be published in PDF and web versions that can be accessed through http://www.transfusionguidelines.org.uk. As important new information emerges, or corrections and amendments to the text are required, these will be published in the electronic versions. Transfusion medicine is changing quickly and it is important to use the up-to-date versions of evidence-based guidelines. Links to key guidelines and other online publications are inserted in the text and a list of key references and useful sources of information are given in Appendix 1. Derek Norfolk August 2013
  15. 15. 1 1 1  Transfusion ten commandments 1
  16. 16. 2
  17. 17. 3 1  Transfusion ten commandments Essentials ■■ Is blood transfusion necessary in this patient? ■■ If so, ensure: •• right blood •• right patient •• right time •• right place. 1 Transfusion should only be used when the benefits outweigh the risks and there are no appropriate alternatives. 2 Results of laboratory tests are not the sole deciding factor for transfusion. 3 Transfusion decisions should be based on clinical assessment underpinned by evidence-based clinical guidelines. 4 Not all anaemic patients need transfusion (there is no universal ‘transfusion trigger’). 5 Discuss the risks, benefits and alternatives to transfusion with the patient and gain their consent. 6 The reason for transfusion should be documented in the patient’s clinical record. 7 Timely provision of blood component support in major haemorrhage can improve outcome – good communication and team work are essential. 8 Failure to check patient identity can be fatal.  Patients must wear an ID band (or equivalent) with name, date of birth and unique ID number. Confirm identity at every stage of the transfusion process. Patient identifiers on the ID band and blood pack must be identical. Any discrepancy, DO NOT TRANSFUSE. 9 The patient must be monitored during the transfusion. 10 Education and training underpin safe transfusion practice. These principles (which are adapted from the NHS Blood and Transplant ‘Transfusion 10 commandments’ bookmark with permission) underpin safe and effective transfusion practice and form the basis for the handbook. 1 Transfusiontencommandments
  18. 18. 5 2 2  Basics of blood groups and antibodies 2
  19. 19. 6
  20. 20. 7 2  Basics of blood groups and antibodies Essentials ■■ ABO-incompatible red cell transfusion is often fatal and its prevention is the most important step in clinical transfusion practice. ■■ Alloantibodies produced by exposure to blood of a different group by transfusion or pregnancy can cause transfusion reactions, haemolytic disease of the fetus and newborn (HDFN) or problems in selecting blood for regularly transfused patients. ■■ To prevent sensitisation and the risk of HDFN, RhD negative or Kell (K) negative girls and women of child-bearing potential should not be transfused with RhD or K positive red cells except in an emergency. ■■ Use of automated analysers, linked to laboratory information systems, for blood grouping and antibody screening reduces human error and is essential for the issuing of blood by electronic selection or remote issue. ■■ When electronic issue is not appropriate and in procedures with a high probability of requiring transfusion a maximum surgical blood ordering schedule (MSBOS) should be agreed between the surgical team and transfusion laboratory. There are more than 300 human blood groups but only a minority cause clinically significant transfusion reactions. The two most important in clinical practice are the ABO and Rh systems. 2.1 Blood group antigens Blood group antigens are molecules present on the surface of red blood cells. Some, such as the ABO groups, are also present on platelets and other tissues of the body. The genes for most blood groups have now been identified and tests based on this technology are gradually entering clinical practice. 2.2 Blood group antibodies These are usually produced when an individual is exposed to blood of a different group by transfusion or pregnancy (‘alloantibodies’). This is a particular problem in patients who require repeated transfusions, for conditions such as thalassaemia or sickle cell disease, and can cause difficulties in providing fully compatible blood if the patient is immunised to several different groups (see Chapter 8). Some antibodies react with red cells around the normal body temperature of 37°C (warm antibodies). Others are only active at lower temperatures (cold antibodies) and do not usually cause clinical problems although they may be picked up on laboratory testing. 2.3 Testing for red cell antigens and antibodies in the laboratory The ABO blood group system was the first to be discovered because anti-A and anti-B are mainly of the IgM immunoglobulin class and cause visible agglutination of group A or B red cells in laboratory mixing tests. Antibodies to ABO antigens are naturally occurring and are found in everyone after the first 3 months of life. Many other blood group antibodies, such 2 Basicsofbloodgroupsandantibodies
  21. 21. 8 Handbook of Transfusion Medicine as those against the Rh antigens, are smaller IgG molecules and do not directly cause agglutination of red cells. These ‘incomplete antibodies’ can be detected by the antiglobulin test (Coombs’ test) using antibodies to human IgG, IgM or complement components (‘antiglobulin’) raised in laboratory animals. The direct antiglobulin test (DAT) is used to detect antibodies present on circulating red cells, as in autoimmune haemolytic anaemia or after mismatch blood transfusion. Blood group antibodies in plasma are demonstrated by the indirect antiglobulin test (IAT). Nearly all clinically significant red cell antibodies can be detected by an IAT antibody screen carried out at 37°C (see section 2.7). 2.4 The ABO system There are four main blood groups: A, B, AB and O. All normal individuals have antibodies to the A or B antigens that are not present on their own red cells (Table 2.1). The frequency of ABO groups varies in different ethnic populations and this must be taken into account when recruiting representative blood donor panels. For example, people of Asian origin have a higher frequency of group B than white Europeans. Individuals of blood group O are sometimes known as universal donors as their red cells have no A or B antigens. However, their plasma does contain anti-A and anti-B that, if present in high titre, has the potential to haemolyse the red cells of certain non-group O recipients (see below). Table 2.1  Distribution of ABO blood groups and antibodies Blood group Antigens on red cells Antibodies in plasma UK blood donors O none anti-A and anti-B 47% A A anti-B 42% B B anti-A 8% AB A and B none 3% 2.4.1 Transfusion reactions due to ABO incompatibility ABO-incompatible red cell transfusion is often fatal and its prevention is the most important step in clinical transfusion practice (Chapter 5). Anti-A and/or anti-B in the recipient’s plasma binds to the transfused cells and activates the complement pathway, leading to destruction of the transfused red cells (intravascular haemolysis) and the release of inflammatory cytokines that can cause shock, renal failure and disseminated intravascular coagulation (DIC). The accidental transfusion of ABO-incompatible blood is now classified as a ‘never event’ by the UK Departments of Health. Transfusion of ABO-incompatible plasma containing anti-A or anti-B, usually from a group O donor, can cause haemolysis of the recipient’s red cells, especially in neonates and small infants. Red cells stored in saline, adenine, glucose and mannitol (SAG-M) additive solution (see Chapter 3) contain less than 20 mL of residual plasma so the risk of haemolytic reactions is very low. Group O red cell components for intrauterine transfusion, neonatal exchange transfusion or large-volume transfusion of infants are screened to exclude those with high-titre anti-A or anti-B. Group O plasma-rich blood components such as fresh frozen plasma (FFP) or platelet concentrates should not be given to patients of group A, B or AB if ABO-compatible components are readily available (Table 2.2).
  22. 22. 9 2  Basics of blood groups and antibodies Cryoprecipitate contains very little immunoglobulin and has never been reported to cause significant haemolysis. In view of the importance of making AB plasma readily available, AB cryoprecipitate manufacture and availability is a low priority for the UK Blood Services. Table 2.2  Choice of group of red cells, platelets, fresh frozen plasma (FFP) and cryoprecipitate according to recipient’s ABO group Patient’s ABO group Red cells Plateletsa Fresh frozen plasma (FFP)b Cryoprecipitate O First choice O O O O Second choice A A or B A or B Third choice AB A First choice A A A A Second choice Oc Od AB O or B Third choice Bd B First choice B Ad B B Second choice Oc Od AB O or A Third choice Ad AB First choice AB Ad AB AB Second choice A or B Od Ad A or B Third choice Oc Bd O a Group B or AB platelets are not routinely available b Group AB FFP is often in short supply c Screening for high-titre anti-A and anti-B is not required if plasma-depleted group O red cells in SAG-M are used d Tested and negative for high-titre anti-A and anti-B 2.5 The Rh system There are five main Rh antigens on red cells for which individuals can be positive or negative: C/c, D and E/e. RhD is the most important in clinical practice. Around 85% of white Northern Europeans are RhD positive, rising to virtually 100% of people of Chinese origin. Antibodies to RhD (anti-D) are only present in RhD negative individuals who have been transfused with RhD positive red cells or in RhD negative women who have been pregnant with an RhD positive baby. IgG anti-D antibodies can cause acute or delayed haemolytic transfusion reactions when RhD positive red cells are transfused and may cause haemolytic disease of the fetus and newborn (HDFN – see Chapter 9). It is 2 Basicsofbloodgroupsandantibodies
  23. 23. 10 Handbook of Transfusion Medicine important to avoid exposing RhD negative girls and women of child-bearing potential to RhD positive red cell transfusions except in extreme emergencies when no other group is immediately available. 2.6 Other clinically important blood group systems Alloantibodies to the Kidd (Jk) system are an important cause of delayed haemolytic transfusion reactions (see Chapter 5). Kell (anti-K) alloantibodies can cause HDFN and it is important to avoid transfusing K positive red cells to K negative girls and women of child- bearing potential. Before red cell transfusion, the plasma of recipients is screened for clinically important red cell alloantibodies so that compatible blood can be selected. 2.7 Compatibility procedures in the hospital transfusion laboratory 2.7.1 Group and screen The patient’s pre-transfusion blood sample is tested to determine the ABO and RhD groups and the plasma is screened for the presence of red cell alloantibodies capable of causing transfusion reactions. Antibody screening is performed using a panel of red cells that contains examples of the clinically important blood groups most often seen in practice. Blood units of a compatible ABO and Rh group, negative for any blood group alloantibodies detected, can then be selected from the blood bank, taking into account any special requirements on the transfusion request such as irradiated or cytomegalovirus (CMV) negative components. Almost all hospital laboratories carry out blood grouping and antibody screening using automated analysers with computer control of specimen identification and result allocation. This is much safer than traditional manual techniques and eliminates most transcription and interpretation errors. ABO grouping is the single most important test performed on pre-transfusion samples and the sensitivity and security of testing systems must never be compromised. Robust identification procedures outside the laboratory at patient blood sampling, collection of blood from the blood bank and administration of blood at the bedside are vital (see Chapter 4). The current British Committee for Standards in Haematology (BCSH) guideline for pre-transfusion compatibility procedures (2012) recommends that a second sample should be requested for confirmation of the ABO group of a first-time transfused patient provided this does not impede the delivery of urgent red cells or components (http://www.bcshguidelines.com). 2.7.2 Compatibility testing Traditionally, the final step in providing safe blood is to carry out a serological crossmatch between the patient’s plasma and a sample of red cells from the units of blood selected for transfusion. This is performed by the IAT method at 37°C, looking for evidence of a reaction that would indicate incompatibility.
  24. 24. 11 2  Basics of blood groups and antibodies 2.7.3 Electronic issue This is sometimes known as computer crossmatching. Most hospitals now issue the majority of blood by this safe and rapid technique. It relies on the fact that if the patient’s ABO and RhD groups are reliably established, and a sensitive antibody screen is negative, the possibility of issuing incompatible blood is negligible. The laboratory computer can identify all compatible units in the blood bank inventory without the need for further testing. National guidelines require the use of automated testing systems interfaced with laboratory information systems before electronic selection is used and all results must be transmitted electronically to remove human error. Electronic issue should not be used: ■■ If the patient’s plasma contains, or has been known to contain, red cell alloantibodies of clinical significance ■■ If the antibody screen is positive ■■ If the patient has had an ABO-incompatible marrow or haemopoietic stem cell transplant ■■ If the patient has had an ABO-incompatible solid organ transplant in the last 3 months ■■ For neonates or fetuses, if the mother has an IgG red cell antibody present in her plasma. 2.7.4 Blood for planned procedures Many operations rarely need transfusion. As long as the laboratory can provide components quickly in an emergency, there is no need to reserve blood units in the blood bank. Group and screen and electronic issue are now widely used in this situation and allow more efficient use of blood stocks and laboratory scientist time. Patients undergoing planned procedures that may require transfusion, such as major surgery, ideally have samples for group and screen taken at preadmission clinics. Problems in providing compatible blood are then identified before admission to hospital. There is a (usually small) risk that the patient may develop new blood group alloantibodies between the time of initial testing and the date of operation, especially if they have recently been transfused or become pregnant. Having reviewed current evidence, the BCSH guidelines for pre-transfusion compatibility procedures (Milkins et al., 2012) made the following pragmatic recommendations for timing of pre-transfusion blood samples: ■■ Testing should be performed on samples collected no more than 3 days in advance of the transfusion when the patient has been transfused or become pregnant within the preceding 3 months. ■■ An extension to 7 days may be considered for regularly/frequently transfused patients with no alloantibodies and pregnant women with no significant alloantibodies who need to have blood standing by for a potential obstetric emergency such as placenta praevia. Remote issue of compatible blood components from satellite blood refrigerators electronically linked to the laboratory computer system allows safe and efficient provision of blood when the transfusion laboratory and operating theatres are on different hospital sites. Successful adoption of this approach requires close collaboration with the clinical team and clear local guidelines and policies. When electronic issue is not available or appropriate and in procedures with a high probability of requiring transfusion a maximum surgical blood ordering schedule (MSBOS) should be agreed between the surgical team and transfusion laboratory. This specifies how many blood units will be routinely reserved (in the blood bank or satellite refrigerator) for standard procedures, based on audits of local practice. When developing an MSBOS it is usual to aim for a crossmatched to transfused ratio of no more than 3:1 and actual blood use should be audited and reviewed at regular intervals. 2 Basicsofbloodgroupsandantibodies
  25. 25. 12
  26. 26. 13 3 3 Providing safe blood 3
  27. 27. 14
  28. 28. 15 3  Providing safe blood Essentials ■■ Unpaid volunteers, donating regularly, are key to the provision of safe and sufficient blood for transfusion. ■■ 17 to 65 year olds can enrol as first-time blood donors and there is no upper age limit for regular donors (subject to an annual health check). ■■ To ensure the safety of the donor and recipient, a medical questionnaire covering health, lifestyle, travel history, medical history and medication is completed before each donation. ■■ The minimum mandatory infection screen on all donations is for hepatitis B and C, HIV, HTLV and syphilis, and extra tests are performed as required. ■■ The risk of transmission of prion diseases such as variant Creutzfeldt–Jakob disease (vCJD) is reduced by excluding at-risk donors (including recipients of a blood transfusion or tissue/organ transplant since 1980), removing white cells from donations (leucodepletion), importing plasma derivatives from countries with a low risk of vCJD and providing imported, virus-inactivated fresh frozen plasma (FFP) for patients born on or after 1 January 1996. ■■ Donations are routinely ABO and RhD typed and screened for clinically important blood group antibodies. ■■ Modern transfusion practice is based on the use of blood components rather than whole blood donations. ■■ Plasma derivatives are licensed medicines and include albumin solutions, coagulation factor concentrates and immunoglobulins. Blood transfusion in the UK is now very safe indeed and most serious adverse events originate in the hospital rather than the blood transfusion centre (see Chapter 5). However, ensuring a safe and effective blood supply remains essential. This requires a combination of high-quality donor recruitment and selection, infection screening, serological testing and blood component production (followed by rational clinical use). The four UK Blood Services – NHS Blood and Transplant, Northern Ireland Blood Transfusion Service, Scottish National Blood Transfusion Service and Welsh Blood Service – maintain common standards for blood donation, testing and blood products. The Joint UKBTS Professional Advisory Committee (JPAC) is responsible for producing the Guidelines for the Blood Transfusion Services in the UK, often known as the Red Book (http://www.transfusionguidelines.org.uk/). In 2011 the UK Blood Services issued 2.1 million units of red cells, 300 000 platelet doses, 288 000 units of fresh frozen plasma and 126 000 units of cryoprecipitate. 3.1 Blood donation Unpaid volunteers who donate on a regular basis are a crucial element in the provision of a safe and reliable supply of blood. Many studies show that altruistic donors have a lower prevalence of transfusion-transmissible infections. The minimum age for donation is 17 years. There is no upper age limit for regular donors, although they are subject to annual health review after their 66th birthday. The upper age limit for first-time donors is 65 years. The minimum body weight for blood donation is 50 kg (7 st 12 lb). Only 5% of eligible people are regular blood donors and the Blood Services put much effort into improving recruitment, especially of donors from minority ethnic groups. 3 Providingsafeblood
  29. 29. 16 Handbook of Transfusion Medicine 3.1.1 Donor eligibility Donors answer a series of questions before each donation relating to their health, lifestyle, travel history, medical history and medication. This is to ensure the safety of both the donor and recipients. Donor exclusion and deferral criteria are regularly reviewed in the light of scientific knowledge. For example, there have been recent significant changes to the eligibility of ‘men who have sex with men’ (MSM) to donate blood in the UK (see Chapter 5). Up-to- date eligibility criteria are given in the Red Book (http://www.transfusionguidelines.org.uk/). 3.1.2 Frequency of donation The normal interval between whole blood donations is 16 weeks (minimum 12 weeks) but no more than three donations a year are collected from female donors because of their more precarious iron status. Donors undergo a screening test for anaemia, usually the copper sulphate flotation test on a finger prick sample. The minimum pre-donation Hb concentration is 125 g/L for female donors and 135 g/L for males. Donors giving double red cell donations by apheresis must have a pre-donation Hb concentration of 140 g/L and the minimum interval between donations is 26 weeks. Donors can give platelets or plasma by apheresis on a cell separator with a maximum of 24 procedures in 12 months. The minimum interval between donations is 2 weeks and plasma donors are limited to 15 litres a year. 3.1.3 Genetic haemochromatosis Donors with this common genetic condition, which causes increased iron absorption from the diet, are eligible to become blood donors if they meet all the other medical selection and age criteria. Regular blood donation can be part of their maintenance treatment schedule to prevent iron overload. 3.2 Tests on blood donations 3.2.1 Screening for infectious agents At each donation, the following mandatory tests are performed: ■■ Hepatitis B – HBsAg ■■ Human immunodeficiency virus – anti-HIV 1 and 2 and HIV NAT (nucleic acid testing) ■■ Hepatitis C – anti-HCV and HCV NAT ■■ Human T-cell lymphotropic virus – anti-HTLV I and II ■■ Syphilis – syphilis antibodies. Some donations are tested for cytomegalovirus (CMV) antibodies to provide CMV negative blood for patients with certain types of impaired immunity (see Chapter 5). Additional tests, performed in special circumstances, include: ■■ Malarial antibodies ■■ West Nile Virus antibodies ■■ Trypanosoma cruzi antibodies.
  30. 30. 17 3  Providing safe blood 3.2.2 Precautions to reduce the transfusion transmission of prion-associated diseases These include variant Creutzfeldt–Jakob disease (vCJD – caused by the same agent as bovine spongioform encephalopathy (BSE) in cattle – ‘mad cow disease’) and sporadic or inherited CJD. The following are permanently deferred from blood donation: ■■ Persons who have received a blood transfusion or tissue/organ transplant from a donor since 1980 ■■ Anyone who has received human pituitary-derived hormones, grafts of human dura mater or cornea, sclera or other ocular tissue ■■ Members of a family at risk of inherited prion diseases ■■ Persons notified that they may be at increased risk of vCJD due to possible exposure to an infected individual by surgical instruments, blood product transfusion or transplant of tissues or organs ■■ Persons notified that they may be at increased risk because a recipient of their blood or tissues has developed a prion-related disorder. More information, including the latest data on transfusion-transmitted vCJD, can be obtained from the National CJD Research and Surveillance Unit (http://www.cjd.ed.ac.uk/index.html). 3.2.3 Blood groups and blood group antibodies Every donation is tested to determine the ABO and RhD group of the red cells and the plasma is screened to detect the most common blood group antibodies that might cause problems in a recipient. Some donations are tested for a wider range of clinically significant blood groups (extended phenotyping) to allow closer matching and reduce the development of alloantibodies in patients who need long-term red cell transfusion support (see Chapter 8). Blood for neonatal or intrauterine use has a more extensive antibody screen (see Chapter 10). Some group O donations are screened for high levels of anti-A and anti-B antibodies to reduce the risk of haemolytic reactions when group O plasma, platelets or other components containing a large amount of plasma (e.g. red cells for intrauterine or neonatal exchange transfusion) are transfused to group A, B or AB patients, especially neonates and infants. 3.2.4 Molecular blood group testing The genes for most human blood groups have now been identified. Currently only a limited number of patients undergo genotyping. These include recently transfused patients whose blood group is uncertain and fetuses that require typing to define the risk from maternal antibodies. Routine DNA testing/genotyping using rapid automated technology is likely to enter blood service and hospital laboratory practice in the next decade. 3.3 Blood products These are classified as blood components prepared in the blood transfusion centre (red cells, platelets, fresh frozen plasma and cryoprecipitate) or plasma derivatives manufactured from pooled plasma donations in plasma fractionation centres (such as albumin, coagulation factors and immunoglobulins). Plasma derivatives are covered by the Medicines Act and, like any other drug, must be prescribed by a licensed practitioner. Since 1999, as a vCJD risk-reduction measure, all plasma derivatives used in the UK are manufactured using donations from countries with a low risk of vCJD. 3 Providingsafeblood
  31. 31. 18 Handbook of Transfusion Medicine 3.3.1 Blood components Whole blood is now rarely used for transfusion. Blood component therapy makes clinical sense as most patients require a specific element of blood, such as red cells or platelets, and the dose can then be optimised. Each component is stored under ideal conditions (e.g. red cells must be refrigerated, platelets must not) and the use of precious blood donations becomes more efficient. The use of blood components in clinical practice is covered in Chapters 7 to 10. The process of producing blood components and plasma derivatives is summarised in Figure 3.1. 3.3.2 Labelling of blood components 3.3.2.1 Blood component labels The content of blood pack labels attached at the transfusion centre is prescribed by the Blood Safety and Quality Regulations 2005 (BSQR). Key information is present in both eye-readable and barcoded form and allows the donor origin (via a unique donation number) and processing steps of the product to be traced as well as indicating the blood group, any special requirements (such as CMV negative or irradiated), expiry date and storage conditions. Work is in progress to review the content of blood component labels and improve their clarity. Up-to-date information is available in the Guidelines for the Blood Transfusion Services in the UK (http://www.transfusionguidelines.org.uk). 3.3.2.2 Blood compatibility labels These are attached to the pack in the hospital transfusion laboratory and uniquely identify the patient for whom the component has been selected. At the final bedside check, the donation number and other details on the compatibility label must match those on the blood pack label and the patient details must exactly match those on the recipient’s ID band (see Chapter 4 for detailed discussion of safe blood administration). 3.3.2.3 Specifications of blood components Whole blood donations of 405–495 mL (mean 470 mL) are collected into 63 mL of citrate phosphate dextrose (CPD) anticoagulant. All blood donations are filtered to remove white blood cells (pre-storage leucodepletion) to leave 1×106 leucocytes in the pack. This was introduced in 1998 as a vCJD risk-reduction measure but also reduces the incidence of febrile transfusion reactions and alloimmunisation to white cell (including HLA) antigens. Indicative contents of commonly available components are noted below, based on quality assurance data from NHS Blood and Transplant (see http://www.blood.co.uk/hospitals/ products for more detail and an up-to-date compendium). Blood components for neonates and intrauterine transfusion are discussed in Chapter 10.
  32. 32. 19 3  Providing safe blood Figure 3.1  Production of blood components and blood derivatives Pooled platelets Red cells Fresh frozen plasma Plasma derivatives, e.g. albumin, immunoglobin NB: platelet shelf life can be extended to 7 days with use of bacterial screening 36 months 35 days 5 days4ºC 22ºC –25ºC Plateletpheresis Process into blood components Filter to remove leucocytes Plasma (from non-UK source) Fractionation Confirm compatibility Patient (Pool) (Thaw) Education Recruitment Selection Donation Test for: HIV Hepatitis B Hepatitis C HTLV Syphilis ABO + RhD Other phenotypes Red cell antibodies (CMV, Hbs, malaria) 3 Providingsafeblood
  33. 33. 20 Handbook of Transfusion Medicine Red cells These are used to restore oxygen carrying capacity in patients with anaemia or blood loss where alternative treatments are ineffective or inappropriate. They must be ABO compatible with the recipient (see Table 2.2). Clinical indications for red cell transfusion are discussed in Chapters 7 to 10. Red cells in additive solution In red cells in additive solution (Table 3.1) the majority of plasma is removed and replaced by 100 mL saline, adenine, glucose and mannitol additive solution (SAG-M). Table 3.1  Red cells in additive solution Volume (mL) 220–340 Haematocrit (L/L) 0.5–0.7 Haemoglobin content (g) 40 (in more than 75% of units tested) Residual plasma (mL) 5–30 Storage temperature 2–6°C Shelf life Up to 35 days from donation Irradiated red cells Irradiated red cells are indicated for patients at risk of transfusion-associated graft-versus- host disease (TA-GvHD – see Chapter 8). The component must be irradiated by gamma or X-rays within 14 days of donation and it then has a shelf life of 14 days from irradiation. Washed red cells Indicated for patients with recurrent or severe allergic or febrile reactions to red cells, and severely IgA-deficient patients with anti-IgA antibodies for whom red cells from an IgA- deficient donor are not available (see Chapter 5). They are produced either manually (24‑hour shelf life) or by a closed, automated system in which the red cells are sequentially washed to remove most of the plasma (0.5 g residual plasma per unit) and then resuspended in 100 mL SAG-M (shelf life 14 days from washing). Platelets Platelet transfusion is indicated for the treatment or prevention of bleeding in patients with a low platelet count (thrombocytopenia) or platelet dysfunction. An adult therapeutic dose (ATD) of platelets is 240×109 per transfusion. Platelets have ABO antigens on their surface and may have reduced survival if transfused to an ABO-incompatible recipient, although this is not usually clinically significant. They are usually only available in groups O, A or B, with only a small number of group AB platelets produced. Anti-A or anti-B antibodies in the plasma of platelet components may rarely cause haemolysis of the recipient’s red cells, especially in babies and small children. Group O platelets should ideally only be given to group O recipients. Selection of platelets for patients of other ABO groups is summarised in Table 3.2. RhD negative platelet concentrates should be given to RhD negative patients where possible, especially to RhD negative women of child-bearing potential. When RhD-incompatible platelets have to be given, administration of anti-D immunoglobulin may prevent immunisation.
  34. 34. 21 3  Providing safe blood Platelets are produced in two ways (see Tables 3.2 and 3.3): ■■ Whole blood donations are centrifuged and the buffy coats (between the red cell and plasma layers) from four donations are pooled in the plasma of one of the donors (male, to reduce the risk of transfusion-related acute lung injury (TRALI) – see Chapter 5). ■■ An ATD of platelets is obtained from a single donor by apheresis (donors may give two or three ATDs at a single session). The UK Blood Services aim to provide more than 80% of platelet doses by apheresis to reduce the exposure of patients to multiple donors (a vCJD risk-reduction measure). Platelets are stored in temperature-controlled incubators (20–24°C) with constant agitation (refrigerated platelets are rapidly removed from the circulation). The recent introduction of automated bacterial screening has allowed some Blood Services to extend the shelf life from 5 to 7 days after donation. Table 3.2  Platelets from pooled buffy coats Number of donors per pack 4 Mean volume (mL) 300 Mean platelets (×109 per unit) 308 (range 165–500) Anticoagulant CPD Storage 20–24°C with agitation Shelf life 5 days (7 days if bacterial screening) Table 3.3  Platelets from apheresis donation Number of donors per pack 1 Mean volume (mL) 199 Mean platelets (×109 per unit) 280 (range 165–510) Anticoagulant Acid citrate dextrose Storage 20–24°C with agitation Shelf life 5 days (7 days if bacterial screening) Irradiated platelets Platelets may be irradiated to prevent TA-GvHD in susceptible patients. They retain their normal shelf life. Platelets in additive solution After ‘washing’ to remove most of the plasma the platelets are resuspended in 200 mL of platelet additive solution (PAS). This component is indicated for patients with recurrent severe allergic or febrile reactions to standard platelet transfusions. The shelf life is reduced to 24 hours after preparation and they must be ordered specially from the Blood Service. Some platelets are lost in the washing process and the component still contains around 10 mL residual plasma. 3 Providingsafeblood
  35. 35. 22 Handbook of Transfusion Medicine Human leucocyte antigen (HLA)-selected platelets Indicated for patients refractory to random platelet components because of the development of HLA antibodies after previous transfusions (see Chapter 9). The Blood Services maintain a panel of HLA-typed platelet donors who donate by apheresis. The platelets are irradiated before issue to prevent TA-GvHD. Human platelet antigen (HPA)-selected platelets HPA-1a/5b negative platelets are kept in limited numbers at strategically placed stock‑holding units in the UK and are used for babies with neonatal alloimmune thrombocytopenia (NAIT) (see Chapter 10). Plasma Plasma is obtained from whole blood donations or component donation by apheresis. Only male donors are used to reduce the risk of TRALI. The UK Departments of Health recommend that patients born on or after 1 January 1996 should only receive plasma sourced from countries with a low risk of vCJD. Imported plasma is treated with a pathogen reduction process, such as methylene blue or solvent detergent treatment, to reduce the risk of viral transmission. Plasma components of the same ABO group should be transfused to patients wherever possible. If ABO-identical plasma is not available, the selection criteria given in Table 2.2 are recommended. Plasma components do not need to be matched for RhD group as they contain no red cells or red cell stroma. They do not cause TA-GvHD and irradiation is not required. Fresh frozen plasma (FFP) Plasma is frozen soon after collection to maintain the activity of blood-clotting factors. It can be stored for up to 36 months at –25°C or below. Standard UK FFP is issued as single-donor packs which must be thawed before use, usually in a purpose-designed waterbath. Thawed units of FFP can be stored for up to 24 hours at 4°C before transfusion. Clotting factor levels vary widely between normal healthy donors and this variability is reflected in the concentrations found in individual packs of FFP. FFP (see Table 3.4) is indicated for the treatment of patients with bleeding due to multiple clotting factor deficiencies such as disseminated intravascular coagulation (DIC). It may also be used in patients with inherited clotting factor deficiencies (e.g. Factor V deficiency) where a clotting factor concentrate is not yet available. The recommended dose is 12–15 mL/kg (minimum of four units in a 70 kg adult). However, much larger doses may be needed to produce ‘therapeutic’ levels of coagulation factors and volume overload is a significant clinical problem. FFP is no longer indicated for the reversal of warfarin, as a specific and effective antidote is available (prothrombin complex). FFP carries a significant risk of severe allergic reactions (see Chapter 5) and should not be used as a plasma volume expander. Table 3.4  Fresh frozen plasma Number of donor exposures per pack 1 Mean volume (mL) 274 Mean Factor VIIIc (IU/mL) 0.83 (specification 0.7) Anticoagulant CPD Storage –25°C Shelf life 36 months (24 hours at 4°C after thawing)
  36. 36. 23 3  Providing safe blood Pathogen-inactivated fresh frozen plasma Solvent detergent treated FFP (SD-FFP) is available as a licensed medicinal product (Octaplas® , Table 3.5). It is prepared from pools with a maximum of 1520 donations and the SD process inactivates bacteria and most encapsulated viruses, including hepatitis B and C and HIV. Donations are sourced from countries with a low risk of vCJD and a prion- reduced version, Octaplas LG® , is now licensed in the UK. The pooling process leads to more standardised concentrations of clotting factors in each pack and probably explains the significantly reduced incidence of severe allergic reactions and TRALI in haemovigilance reports. SD treatment reduces the concentration of fibrinogen and Factor VIIIc by 15–20%, but levels remain within the defined specification. Levels of Protein S, an anticoagulant factor, are around 30% lower and this may be important in patients with an increased risk of thromboembolism. UK guidelines recommend imported SD-FFP for plasma exchange in patients with thrombotic thrombocytopenic purpura (TTP – see Chapter 11). Table 3.5  Solvent detergent plasma (Octaplas® ) Number of donor exposures per pack Maximum 1520 donors per batch Volume (mL) 200 (standardised) Mean Factor VIIIc (IU/mL) 0.8 (specification 0.5) Mean fibrinogen (mg/mL) 2.6 (range 1.5–4.0) Anticoagulant Sodium citrate Storage –18°C Shelf life 4 years (transfuse immediately after thawing) Based on data from Octapharma AG (http://www.octapharma.co.uk) Methylene blue treated FFP (MB-FFP) is a single-donor pathogen-reduced component available through the UK Blood Services. The process inactivates encapsulated viruses and bacteria. In the UK, the methylene blue process is used to treat packs of FFP imported from low vCJD risk countries, providing a single-donor component that is preferred by some neonatologists and paediatricians. MB-FFP has a reduced activity of fibrinogen and Factor VIII. The clinical significance of this is uncertain, although some studies in cardiac surgery have suggested the need for bigger transfusions to achieve the same therapeutic effect. Like all single-donor FFP components, the content of clotting factors varies between individual packs. Cryoprecipitate Cryoprecipitate (Table 3.6) is made by thawing UK donor FFP at 4°C, producing a cryoglobulin rich in fibrinogen, Factor VIII and von Willebrand factor. It was developed as a treatment for haemophilia but this use has now been replaced by Factor VIII concentrate. Cryoprecipitate is mainly used as a more concentrated, hence lower volume for infusion, source of fibrinogen than FFP. It is available from the Blood Services as single-donor packs or as pools of five donations. The recommended adult therapeutic dose is two pools of five units (or one unit per 5–10 kg body weight), which will typically raise the plasma fibrinogen by about 1 g/L. Cryoprecipitate produced from imported MB-FFP is now available. Because of a lower concentration of fibrinogen, pools of six donations are issued. 3 Providingsafeblood
  37. 37. 24 Handbook of Transfusion Medicine Table 3.6  Cryoprecipitate Cryoprecipitate packs Cryoprecipitate pools Number of donors 1 5 Mean volume (mL) 43 189 Fibrinogen (mg/pack) 396 (specification 140) 1552 (specification 700) Factor VIIIc (IU/pack) 105 (specification 70) 454 (specification 350) Storage –25°C –25°C Shelf life 36 months (use within 4 hours of thawing, do not refrigerate) 36 months (use within 4 hours of thawing, do not refrigerate) Granulocytes Although their clinical effectiveness is controversial, transfusion of granulocytes (neutrophils – phagocytic white blood cells) may be indicated in patients with life-threatening soft tissue or organ infection with bacteria or fungi and low neutrophil counts, usually in the setting of severe, prolonged neutropenia after cytotoxic chemotherapy. There are two main granulocyte-rich components available: buffy coats derived from whole blood donations and granulocytes collected by apheresis from individual donors. Because of contaminating red cells, granulocyte components must be ABO and RhD compatible and crossmatched with the recipient. They are irradiated before issue to prevent TA-GvHD. Daily transfusions are given, with monitoring of response, until recovery of bone marrow function. Individual buffy coats These buffy coats (Table 3.7) contain large numbers of red cells and the Hb/haematocrit of the recipient must be monitored. Usefully, the high platelet content may reduce the need for platelet transfusions. The recommended dose is ten buffy coats daily for adults (10–20 mL/kg for smaller children and infants). Table 3.7  Buffy coat (granulocytes) Mean volume per pack (mL) 60 (10 packs = 600 mL) Mean granulocytes (×109 /pack) 1.0 (10 packs = 1×1010 ) Haematocrit (L/L) 0.45 Platelets (×109 /pack) 70 Storage 20–24°C Shelf life To midnight on day of collection Pooled buffy coats (granulocytes pooled buffy coat derived in additive solution and plasma) This component (see Table 3.8) was introduced in the UK in 2012. Although the manufacturing process is more complicated, it has the advantages of lower volume, less red cell and plasma contamination and resuspension in male donor plasma and additive solution to reduce the risk of TRALI. The dose is two packs (20 donations) for an adult and 10–20 mL/kg for children.
  38. 38. 25 3  Providing safe blood Table 3.8  Granulocytes pooled buffy coat derived in additive solution and plasma Mean volume per pack (mL) 207 (175–250) mL Mean granulocytes (×1010 /pack) 1.0 (1×1010 ) Haematocrit (L/L) 0.15 Platelets (×109 /pack) 499 (equivalent to 2.5 adult transfusion doses) Storage 20–24°C (not agitated) Shelf life To midnight on day following collection Apheresis granulocytes The collection of a therapeutic dose of apheresis granulocytes (Table 3.9) requires the donor to be pre-treated with steroids and/or injections of granulocyte colony stimulating factor (G-CSF). Hence, their collection is restricted to directed donors (usually a relative) for an individual patient, rather than UK Blood Service volunteer donors, and the component is only available in certain clinical centres. Table 3.9  Apheresis granulocytes Mean volume per unit (mL) 312 Granulocytes per unit 1×1010 Haematocrit (L/L) 0.23 Platelets (×109 per unit) 111 Storage 20–24°C Shelf life 24 hours from collection Plasma derivatives These are licensed medicinal products manufactured from human plasma donations. Some of the main products used in hospital practice are listed below but the reader is referred to the British National Formulary (BNF – http://bnf.org/bnf) and the individual Summary of Product Characteristics for more detailed information about formulation and clinical indications. Although these products are manufactured from large donor pools, sometimes thousands of donations, all now undergo multiple pathogen inactivation steps to eradicate transfusion-transmitted viruses. Since 1999, all plasma derivatives used in the UK are derived from imported plasma (a vCJD risk-reduction measure). Human albumin solution Human albumin solution (HAS) contains no clotting factors or blood group antibodies and crossmatching is not required. The clinical indications for HAS are controversial. Crystalloid solutions or synthetic colloidal plasma substitutes are alternatives for use as plasma expanders in acute blood or plasma loss. HAS should not be used to ‘correct’ the low serum albumin level often associated with acute or chronic illness. Side effects include occasional severe hypersensitivity reactions. HAS is available in two forms: ■■ Isotonic solutions (4.5 and 5.0% in volumes of 50 to 500 mL): Often used to replace subacute plasma volume loss caused by burns, pancreatitis or trauma, and as a replacement fluid in plasma exchange. 3 Providingsafeblood
  39. 39. 26 Handbook of Transfusion Medicine ■■ Concentrated solutions (20% in volumes of 50 and 100 mL): Indications may include initiating diuresis in hypoalbuminaemic patients with liver cirrhosis or nephrotic syndrome, removal of large volumes of ascites in patients with portal hypertension and to assist the reduction of high bilirubin levels by exchange transfusion in the newborn (unconjugated bilirubin binds to albumin). Clotting factor concentrates Single-factor concentrates are available for the treatment of most inherited coagulation deficiencies except Factor V and Factor II (prothrombin). Most patients in the UK with severe haemophilia A are now treated with recombinant Factor VIIIc, which carries no risk of viral or prion transmission. Fibrinogen concentrate (Factor I) is, at present, only licensed in the UK for the treatment of congenital hypofibrinogenaemia but there is encouraging international experience of its effectiveness in the much more common setting of acquired hypofibrinogenaemia (e.g. DIC, traumatic haemorrhage, massive transfusion). Many coagulation experts believe that it will replace the use of cryoprecipitate for this purpose in view of its ease of administration, convenience of storage and standardised fibrinogen content. Prothrombin complex concentrate (PCC) contains Factors II, VII, IX and X. It has replaced FFP as the recommended treatment for rapid reversal of warfarin overdose, with elevated international normalised ratio (INR) and severe bleeding, in view of its superior efficacy, ease of administration and lower risk of severe allergic reactions or fluid overload. Modern formulations of PCC do not contain activated clotting factors and have a low risk of causing thrombotic complications. PCC may also be used to treat bleeding due to the coagulopathy associated with liver disease. The dose for reversal of warfarin is 25–50 IU/kg. Immunoglobulin solutions These are manufactured from large pools of donor plasma: ■■ Normal immunoglobulin: contains antibodies to viruses that are common in the population. Intramuscular normal immunoglobulin may be used to protect susceptible contacts against hepatitis A, measles or rubella. High-dose intravenous immunoglobulin is used as replacement therapy in patients with severe immunoglobulin deficiency and in the treatment of autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP). ■■ Specific immunoglobulins: made from selected donors with high antibody levels to the target of treatment. Examples include tetanus, hepatitis B and rabies immunoglobulins as well as anti-D immunoglobulin for the prevention of maternal sensitisation to RhD in pregnancy (see Chapter 9).
  40. 40. 27 4 4  Safe transfusion – right blood, right patient, right time and right place 4
  41. 41. 28
  42. 42. 29 4  Safe transfusion – right blood, right patient, right time and right place Essentials ■■ Avoid unnecessary and inappropriate transfusions. ■■ Preventable ‘wrong blood into patient’ incidents are nearly always caused by human error and may cause fatal reactions due to ABO incompatibility. ■■ Most mistransfusion incidents are caused by identification errors at the time of pre- transfusion blood sampling, sample handling in the laboratory, collecting the wrong component from the blood bank or transfusion to the patient. ■■ The identity check between patient and blood component is the crucial final opportunity to avoid potentially fatal mistransfusion. ■■ At every stage of the blood administration process the key elements are positive patient identification, excellent communication and good documentation. These can be enhanced by the use of electronic transfusion management systems and barcode technology. ■■ Hospitals should develop local transfusion policies based on national guidelines and ensure all staff involved in the clinical transfusion process are appropriately trained and competency assessed. ■■ Where possible, patients should give ‘valid consent’ for transfusion based on appropriate information and discussion, but signed consent is not a legal requirement. ■■ Non-essential ‘out of hours’ requests for transfusion and overnight administration of blood should be avoided wherever possible because of an increased risk of errors. Data from the UK Serious Hazards of Transfusion (SHOT) initiative (http://www.shotuk.org) show that around 1 in 13 000 blood units are administered to the wrong patient with occasional fatal outcomes. ‘Wrong blood into patient’ incidents are preventable and nearly always caused by human error. The root cause of most incidents is misidentification at the time of pre-transfusion blood sampling, laboratory testing, collecting the blood component from the blood bank or administration of the transfusion at the bedside. Potentially fatal ABO-incompatible transfusions still occur although improved clinical policies, staff training and introduction of methods to improve identification, resulting from the various Better Blood Transfusion initiatives, has significantly reduced their number over the last decade. Avoiding unnecessary or inappropriate transfusions is an essential starting point for safe transfusion practice. The British Committee for Standards in Haematology (BCSH) Guideline on the Administration of Blood Components (2009) (http://www.bcshguidelines.com) describes the essentials of safe requesting, collection and administration of blood components (summarised in Table 4.1) and should form the basis of local transfusion policies. The key principles that underpin every stage of the blood administration process are: ■■ Positive patient identification ■■ Good documentation ■■ Excellent communication. 4 Safetransfusion-rightblood,rightpatient,righttimeandrightplace
  43. 43. 30 Handbook of Transfusion Medicine Table 4.1  Safe blood administration (adapted from the BCSH Guideline on Administration of Blood Components, 2009, with permission) Positive patient identification Positive patient identification at all stages of the transfusion process is essential. Minimum patient identifiers are: •• Last name, first name, date of birth, unique identification number. •• Whenever possible ask patients to state their full name and date of birth. For patients who are unable to identify themselves (paediatric, unconscious, confused or language barrier) seek verification of identity from a parent or carer at the bedside. This must exactly match the information on the identity band (or equivalent). •• All paperwork relating to the patient must include, and be identical in every detail, to the minimum patient identifiers on the identity band. Patient information and consent for transfusion Where possible, patients (and for children, those with parental responsibility) should have the risks, benefits and alternatives to transfusion explained to them in a timely and understandable manner. Standardised patient information, such as national patient information leaflets, should be used wherever possible. Pre-transfusion documentation Minimum dataset in patient’s clinical record: •• Reason for transfusion (clinical and laboratory data). •• Summary of information provided to patient (benefits, risks, alternatives) and patient consent. Prescription (authorisation) The transfusion ‘prescription’ must contain the minimum patient identifiers and specify: •• Components to be transfused •• Date of transfusion •• Volume/number of units to be transfused and the rate or duration of transfusion •• Special requirements (e.g. irradiated, CMV negative). Requests for transfusion Must include: •• Minimum patient identifiers and gender •• Diagnosis, any significant co-morbidities and reason for transfusion •• Component required, volume/number of units and special requirements •• Time and location of transfusion •• Name and contact number of requester. Blood samples for pre-transfusion testing All patients being sampled must be positively identified. •• Collection of the blood sample from the patient into the sample tubes and sample labelling must be a continuous, uninterrupted event involving one patient and one trained and competency assessed healthcare worker. •• Sample tubes must not be pre-labelled. •• The request form should be signed by the person collecting the sample.
  44. 44. 31 4  Safe transfusion – right blood, right patient, right time and right place Collection and delivery of blood component to clinical area •• Before collection, ensure the patient (and staff) is ready to start transfusion and there is good venous access. •• Only trained and competent staff should collect blood from transfusion laboratory or satellite refrigerator. •• Authorised documentation with minimum patient identifiers must be checked against label on blood component. •• Minimum patient identifiers, date and time of collection and staff member ID must be recorded. •• Deliver to clinical area without delay. Administration to patient •• The final check must be conducted next to the patient by a trained and competent healthcare professional who also administers the component. •• All patients being transfused must be positively identified. •• Minimum patient identifiers on the patient’s identity band must exactly match those on blood component label. •• All components must be given through a blood administration set (170–200 µm integral mesh filter). •• Transfusion should be completed within 4 hours of leaving controlled temperature storage. Monitoring the patient Patients should be under regular visual observation and, for every unit transfused, minimum monitoring should include: •• Pre-transfusion pulse (P), blood pressure (BP), temperature (T) and respiratory rate (RR). •• P, BP and T 15 minutes after start of transfusion – if significant change, check RR as well. •• If there are any symptoms or signs of a possible reaction – monitor and record P, BP, T and RR and take appropriate action. •• Post-transfusion P, BP and T – not more than 60 minutes after transfusion completed. •• Inpatients observed over next 24 hours and outpatients advised to report late symptoms (24-hour access to clinical advice). Completion of transfusion episode •• If further units are prescribed, repeat the administration/identity check with each unit. •• If no further units are prescribed, remove the blood administration set and ensure all transfusion documentation is completed. 4.1 Patient identification A patient identification band (or risk-assessed equivalent) should be worn by all patients receiving a blood transfusion. The minimum identifiers on the band are: ■■ Last name ■■ First name ■■ Date of birth 4 Safetransfusion-rightblood,rightpatient,righttimeandrightplace
  45. 45. 32 Handbook of Transfusion Medicine ■■ Unique patient ID number (wherever possible a national number such as the NHS No. in England and Wales, CHI No. in Scotland or HSC No. in Northern Ireland). In emergency situations or where the patient cannot be immediately identified at least one unique identifier, such as AE or trauma number, and patient gender should be used. Wherever possible, patients for blood sampling or transfusion should be asked to state their full name and date of birth and this must exactly match the information on the identification band. To ensure accuracy and legibility, the ID band should be printed from the hospital’s computerised patient administration system, ideally at the bedside. Otherwise, verification of identity should be obtained, if possible, from a parent or carer at the bedside and checked against the identification band. Identification discrepancies at any stage of the transfusion process must be investigated and resolved before moving to the next stage. Identification of patients, samples and blood components throughout the transfusion process can be enhanced by the use of electronic transfusion management systems using barcodes on ID bands and blood components and hand-held scanners linked to the laboratory information systems. Most UK hospitals still use manual ID checks at the bedside although electronic ‘blood-tracking’ systems to control access to blood refrigerators are in more widespread use. 4.2 Documentation The documentation required at each stage of the transfusion process should be kept to an essential minimum and, whether hard copy or electronic, be ‘user-friendly’ to encourage compliance by busy clinical teams. Combined transfusion prescription and monitoring charts or care pathways can be used to record the information and provide a clear audit trail. The development of standardised transfusion documentation in the UK has the potential to reduce errors by clinical staff moving between hospitals. All transfusion documentation should include the minimum patient identifiers. Documentation in the clinical record should include: Pre-transfusion: ■■ The reason for transfusion, including relevant clinical and laboratory data. ■■ The risks, benefits and alternatives to transfusion that have been discussed with the patient and documentation of consent (see below). ■■ The components to be transfused and their dose/volume and rate. ■■ Any special requirements, such as irradiated components. During transfusion: ■■ Details of staff members starting the transfusion. ■■ Date and time transfusion started and completed. ■■ Donation number of the blood component. ■■ Record of observations made before, during and after transfusion. Post-transfusion: ■■ Management and outcome of any transfusion reactions or other adverse events. ■■ Whether the transfusion achieved the desired outcome (e.g. improvement in symptoms, Hb increment).
  46. 46. 33 4  Safe transfusion – right blood, right patient, right time and right place 4.3 Communication Verbal communication between clinical staff and the laboratory risks misunderstanding or transcription error. Written or electronic communication should be used wherever possible although requests for urgent transfusion should be supplemented by telephone discussion with laboratory staff. Good communication is especially important at times of staff handover between shifts, both on the wards and in the laboratory, and can be enhanced by a standardised and documented process. 4.4 Patient consent The Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) recommends that ‘valid consent’ for blood transfusion should be obtained and documented in the clinical record (signed consent for transfusion is not mandatory, but may be a local requirement). This is underpinned by the following recommendations: ■■ Use of standardised sources of information for all patients in the UK – appropriate information leaflets are available from the UK Transfusion Services and should be used in all hospitals. ■■ Use of a standardised information resource for clinicians, indicating the key areas to be discussed when obtaining consent – an example is available from http://www. transfusionguidelines.org.uk/index.asp?Publication=BBTSection=22pageid=7691. ■■ As with any emergency treatment, the need for consent must not prevent or delay essential urgent transfusion, but the presence of a valid Advance Decision Document declining transfusion should always be respected (see Chapter 12). Patients transfused when it is not possible to obtain prior consent should be provided with information retrospectively. This is important, as transfused patients are no longer eligible to act as blood donors. For the same reason, patients who have given consent for possible transfusion during surgery should be informed if they actually received blood while under anaesthesia. ■■ Patients needing long-term transfusion support should have a modified form of consent (e.g. annual review and re-consent) and this should be specified in local policies. 4.5 Authorising (or ‘prescribing’) the transfusion Blood components are not licensed medicines and their ‘prescription’ is not legally restricted to registered medical practitioners. There are clear advantages in terms of safety and efficiency in allowing non-medical practitioners, especially those working in specialist areas such as clinical haematology or oncology, to authorise transfusion in defined situations. A framework has been developed in the UK to allow ‘appropriately trained, competent practitioners’ such as registered nurses and midwives to make the clinical decision and provide the written instruction for blood component transfusion and this is available on http://www.transfusionguidelines.org.uk/docs/pdfs/BTFramework-final010909.pdf. All transfusion ‘prescriptions’ (written authorisation to transfuse) must contain the patient’s minimum identifiers and specify the component, dose/volume, rate of transfusion and any special requirements. It should remain a permanent part of the clinical record. 4 Safetransfusion-rightblood,rightpatient,righttimeandrightplace
  47. 47. 34 Handbook of Transfusion Medicine 4.6 Requests for transfusion Hospital policies should define which clinical staff are authorised to request blood and what training they need. Telephoned requests for blood components should be kept to an essential minimum because of the risk of transcription errors. Non-urgent ‘out of hours’ requests should be avoided wherever possible as SHOT data clearly show an increased risk of errors. Computerised physician order entry (CPOE) systems can reduce errors and provide useful guidance to the requesting clinician. Transfusion requests (whether written or electronic) should contain the following information: ■■ Minimum patient identifiers plus gender (which may be essential for component selection) – BCSH guidelines recommend that organisations have a ‘zero tolerance’ policy for amending or adding to the ‘core identifiers’ once a request is submitted. ■■ Diagnosis and any other clinically relevant information plus the reason for transfusion (not just ‘pre-op’ or ‘anaemia’) as this helps laboratory staff select appropriate components and facilitates audit. This may also be helped by the use of standardised indication codes for transfusion, such as those developed by the English National Blood Transfusion Committee (http://www.transfusionguidelines.org.uk/docs/pdfs/ nbtc_2014_04_recs_indication_codes_2013.pdf). ■■ Time, location and urgency of transfusion. ■■ Relevant information on previous reactions, blood group antibodies or pregnancies. ■■ Type and dose or volume of blood component required. ■■ Any special requirements (e.g. irradiated, CMV negative). 4.7 Pre-transfusion blood sampling Misidentification at blood sampling may lead to fatal ABO-incompatible blood transfusion, especially if the patient has not previously had their blood group documented. Inadequately or mislabelled samples carry a significantly increased risk of containing blood from the wrong patient. Risk of misidentification may be reduced by electronic systems, but all sampling should be carried out in line with the following principles by trained and competent staff: ■■ Patients must be positively identified and their details must match those on the request form. ■■ All inpatients must wear an identity band (or risk-assessed equivalent). ■■ Collection of the sample and labelling of the sample tubes must be performed as one uninterrupted process involving one member of staff and one patient. ■■ Sample tubes must never be pre-labelled. ■■ The sample tube label must contain the minimum patient identifiers (exactly matching those on the request form and identity band), date and time of sampling and identity of person taking the sample. ■■ Labels printed away from the patient (e.g. addressograph labels) must not be used on the transfusion sample but labels printed ‘on demand’ and applied to the tube next to the patient, as used in some electronic ID systems, are acceptable. ■■ All handwritten labels must be legible. ■■ BCSH guidelines recommend that laboratories have a ‘zero tolerance’ policy for rejecting samples that do not meet the above minimum requirements.
  48. 48. 35 4  Safe transfusion – right blood, right patient, right time and right place 4.8 Collection of blood components and delivery to clinical areas Errors in collection are a frequent root cause of wrong blood into patient events. All staff responsible for collecting blood from the transfusion laboratory or satellite refrigerators must be trained and competency assessed according to local policies. Manual documentation of collection, such as a ‘transfusion register’, has been traditionally used but the process can be strengthened by the use of electronic ‘blood-tracking’ systems. ■■ Staff collecting blood must carry documentation, such as a blood collection slip or the transfusion prescription, which contains the minimum patient identifiers. This must be checked against the details on the laboratory-generated label attached to the blood component pack. ■■ Computerised blood-tracking systems using barcodes can check (and record) the identity and accreditation of the person collecting or returning the blood (e.g. by scanning a barcode on their ID badge), ensure that the details on the collection documents match those on the selected blood pack and that the blood is within its expiry time and date. Computer-controlled satellite blood refrigerators are also now available that will only allow access to blood components compatible with the appropriate patient. These are ideal for ‘remote issue’ of blood components at locations without an on-site transfusion laboratory. ■■ The Blood Safety and Quality Regulations (BSQR) require that the time a component is out of a controlled temperature environment is recorded and ‘cold chain’ data must be kept for 15 years. Red cells that have been out of controlled refrigeration for more than 30 minutes must not be reissued for transfusion. (The rationale for the ‘30-minute rule’ is often questioned as it is based on studies carried out many years ago on very different blood components. Recent research shows that red cells show no impairment of function up to 60 minutes out of controlled refrigeration but evidence of bacterial safety is needed before a change in policy can be recommended.) ■■ Emergency group O stock in the blood refrigerator must be clearly identified and separated from units labelled for specific patients. The laboratory must be informed immediately when emergency stock is removed so that it can be replenished and an audit trail maintained. 4.9 Receiving blood in the clinical area Before collecting blood components from the blood bank, the clinical staff should ensure the patient is wearing an identity band and has given consent for transfusion, the transfusion ‘prescription’ has been completed correctly, there is patent venous access and staff are available to start the transfusion promptly and monitor it properly. Only one unit should be collected at a time unless rapid transfusion of large quantities is required (e.g. major haemorrhage). The arrival of components in the clinical area should be documented and the transfusion started as soon as possible. 4 Safetransfusion-rightblood,rightpatient,righttimeandrightplace
  49. 49. 36 Handbook of Transfusion Medicine 4.10 Administration to the patient The identity check between patient and blood component (Figure 4.1) is the final opportunity to avoid potentially fatal mistransfusion (‘the last chance saloon’). The check must be performed for every unit transfused. The key principles of safe bedside administration are: ■■ Blood components must be administered by registered practitioners who are trained and competent according to local policies. ■■ The final check must take place next to the patient, not at the nursing station or another remote area. ■■ There is no evidence that either one or two staff performing the bedside check is safer and local policy should be followed. If two people perform the check, each should perform it independently. ■■ If the checking process is interrupted, it must start again. ■■ Transfusion must only go ahead if the details on the patient identity band (positively confirmed by the patient if possible), the laboratory-generated label attached to the component pack and the transfusion prescription are an exact match. Any discrepancy must immediately be reported to the transfusion laboratory. ■■ Check the expiry date of the component and ensure the donation number and blood group on the pack matches that on the laboratory-generated label attached to the pack. ■■ Any special requirements on the transfusion prescription, such as irradiated component, must be checked against the label on the pack. ■■ Inspect the component pack for signs of leakage, discoloration or clumps. ■■ A ‘compatibility report form’ issued by the laboratory and the patient’s clinical records must not form part of the bedside identity check (‘checking paper against paper’). Compatibility report forms are generated by the same laboratory computer used to produce the laboratory-generated label on the blood pack and the two will always match (even if the blood is being presented to the wrong patient). It is strongly recommended (BCSH and National Patient Safety Agency (www.npsa.nhs.uk)) that laboratories do not issue compatibility report forms to avoid their inappropriate use in the final administration check. ■■ The prescription and other associated paperwork should be signed by the person administering the component and the component donation number, date, time of starting and stopping the transfusion, dose/volume of component transfused and name of the administering practitioner should be recorded in the clinical record. ■■ To reduce the risk of bacterial transmission, blood component transfusions should be completed within 4 hours of removal from a controlled temperature environment. ■■ Non-essential overnight transfusion of blood should be avoided, except in adequately staffed specialist clinical areas, because of the increased risk of errors. 4.11 Monitoring the transfusion episode Transfusion observations should be recorded on a dedicated transfusion record or electronic device that can generate a report for filing in the clinical record. Minimum monitoring of each unit transfused should include: ■■ Regular visual observation of the patient during the transfusion and encouragement to report new symptoms. ■■ Baseline pulse rate, blood pressure (BP), temperature and respiratory rate (RR) must be recorded no more than 60 minutes pre-transfusion.
  50. 50. 37 4  Safe transfusion – right blood, right patient, right time and right place Figure 4.1  Identity check between patient and blood component ■■ Pulse, BP and temperature should be checked around 15 minutes after the start of transfusion (many serious reactions, such as ABO incompatibility or bacterial transmission present early in the transfusion episode). If any of these observations have changed, check RR as well. ■■ If the patient reports new symptoms, repeat the baseline observations and take appropriate action (see Chapter 5). ■■ Check pulse, BP and temperature not more than 60 minutes after the end of the transfusion (and as a baseline before any further units are transfused). ■■ Inpatients should be observed for late reactions over the next 24 hours and day-care patients advised to report symptoms developing after discharge (preferably with issue of a ‘Contact Card’ giving access to immediate clinical advice). 4.12 Technical aspects of transfusion 4.12.1 Intravenous access Blood components can be transfused through most peripheral or central venous catheters, although the flow rate is reduced by narrow lumen catheters and long peripherally inserted central catheters (PICC lines). They should be transfused through an administration set with a 170–200 μm integral mesh filter. Paediatric administration sets with a smaller prime volume are available for small- volume transfusions. Although special platelet administration sets are available, it is safe to use a standard blood administration set, but platelets should not be transfused through a set previously used for red cells as some platelet loss will occur. It is not necessary to prime or flush blood administration sets with physiological (0.9%) saline but a new administration set should be used if blood components are followed by another infusion fluid. Although there is little evidence, current guidelines recommend changing blood administration sets at least every 12 hours to reduce the risk of bacterial infection. Check the laboratory-generated label against the patient’s identity band BLOOD PACK PATIENT’S WRISTBAND Always involve the patient by asking them to state their name and date of birth, where possible SURNAME FORENAME DATE OF BIRTH HOSPITAL NUMBER 4 Safetransfusion-rightblood,rightpatient,righttimeandrightplace
  51. 51. 38 Handbook of Transfusion Medicine Blood and other solutions can be infused through the separate lumens of multi-lumen central venous catheters as rapid dilution occurs in the bloodstream. Where possible, one lumen should be reserved for the administration of blood components. 4.12.2 Infusion devices There are two main types: gravity delivered or infusion pumps. Devices must be CE marked and used according to the manufacturer’s instructions (including the use of compatible administration sets). Infusion devices must be maintained in accordance with the manufacturer’s guidelines and the pre-administration check should include a check of the device and its settings. The device should be monitored regularly during transfusion to ensure the correct volume is being delivered at the correct rate. 4.12.3 Rapid infusion devices These are used in situations such as major haemorrhage. Infusion rates range from 6 to 30 L/hour and most incorporate a blood-warming device. They should be used with a large-gauge venous access catheter. 4.12.4 Blood warmers Rapid infusion of red cells recently removed from the refrigerator may cause hypothermia. Concerns include impaired coagulation in surgical or trauma patients and cardiac arrhythmias if cold blood is transfused rapidly into a central catheter or in neonates and small infants having large-volume transfusions. The National Institute for Health and Care Excellence (NICE) in England recommends that, in all patients undergoing elective or emergency surgery, ‘intravenous fluids (500 mL or more) and blood products should be warmed to 37°C’. Blood warmers may also be used in patients with clinically significant cold antibodies (discuss with a transfusion medicine specialist). Only CE-marked blood warmers should be used. Some operate up to 43°C but are safe if used in accordance with the manufacturer’s instructions. Improvised blood-warming, such as immersion of the pack in hot water, in a microwave or on a radiator must never be used. 4.12.5 Compatible intravenous fluids It is good practice to avoid the co-administration of any intravenous fluid through the same line used for blood components, unless a multi-lumen central venous catheter is used. Solutions containing calcium (e.g. Ringer’s lactate) or calcium-containing colloids (e.g. Haemaccel™ or Gelofusine™) antagonise citrate anticoagulant and may allow clots to form if mixed in the same infusion line. Hypotonic solutions, such as 5% dextrose in water, can cause haemolysis of red cells in laboratory experiments but the clinical significance of this is uncertain and no clinical adverse events have been reported. 4.12.6 Co-administration of intravenous drugs and blood Drugs should never be added to a blood component bag. Wherever possible, intravenous drugs should be administered between transfusions or administered through a second venous access device (or the separate lumen of a multi- lumen central venous catheter). If this is not possible, the transfusion should be temporarily stopped and the line flushed with 0.9% saline before and after administration of the drug.
  52. 52. 39 4  Safe transfusion – right blood, right patient, right time and right place Some patients using patient-controlled analgesia (PCA) devices delivering opioid pain killers, such as those on palliative care or with sickle cell pain crises, have very poor peripheral venous access and it is convenient (and kind) to use the administration line used for transfusion. Standard concentrations of morphine, hydromorphone or meperidine have no harmful effect on co-administered red cells. 4.13 Transfusion of blood components Table 4.2 summarises key points about the transfusion of commonly used components in adult patients (see Chapter 10 for administration of components in paediatric/neonatal practice). Clinical use of blood components is discussed in Chapters 7–10. 4 Safetransfusion-rightblood,rightpatient,righttimeandrightplace
  53. 53. 40 Handbook of Transfusion Medicine Table 4.2  Blood component administration to adults (doses and transfusion rates are for guidance only and depend on clinical indication) (based on BCSH Guideline on the Administration of Blood Components, 2009, with permission) Blood component Notes on administration Red cells in additive solution Transfusions must be completed within 4 hours of removal from controlled temperature storage. Many patients can be safely transfused over 90–120 minutes per unit. A dose of 4 mL/kg raises Hb concentration by approximately 10 g/L. Note: The common belief that one red cell pack = 10 g/L increment only applies to patients around 70 kg weight – the risk of transfusion-associated circulatory overload (TACO) is reduced by careful pre-transfusion clinical assessment and use of single-unit transfusions, or prescription in millilitres, for elderly or small, frail adults where appropriate. During major haemorrhage, very rapid transfusion (each unit over 5–10 minutes) may be required. Platelets One adult therapeutic dose (ATD) (pool of four units derived from whole blood donations or single-donor apheresis unit) typically raises the platelet count by 20–40×109 /L. Usually transfused over 30–60 minutes per ATD. Platelets should not be transfused through a giving-set already used for other blood components. Start transfusion as soon as possible after component arrives in the clinical area. Fresh frozen plasma (FFP) Dose typically 12–15 mL/kg, determined by clinical indication, pre-transfusion and post-transfusion coagulation tests and clinical response. Infusion rate typically 10–20 mL/kg/hour, although more rapid transfusion may be appropriate when treating coagulopathy in major haemorrhage. Because of the high volumes required to produce a haemostatic benefit, patients receiving FFP must have careful haemodynamic monitoring to prevent TACO. FFP should not be used to reverse warfarin (prothrombin complex is a specific and effective antidote). Cryoprecipitate Typical adult dose is two five-donor pools (ten single-donor units). Will raise fibrinogen concentration by approximately 1 g/L in average adult. Typically administered at 10–20 mL/kg/hour (30–60 min per five-unit pool).
  54. 54. 41 5 5  Adverse effects of transfusion 5
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